ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1 This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions. 1. NAME OF THE MEDICINAL PRODUCT Lenalidomide Accord 2.5 mg hard capsules Lenalidomide Accord 5 mg hard capsules Lenalidomide Accord 7.5 mg hard capsules Lenalidomide Accord 10 mg hard capsules Lenalidomide Accord 15 mg hard capsules Lenalidomide Accord 20 mg hard capsules Lenalidomide Accord 25 mg hard capsules 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Lenalidomide Accord 2.5 mg hard capsules Each hard capsule contains 2.5 mg of lenalidomide. Excipient with known effect Each hard capsule contains 36 mg of lactose. Lenalidomide Accord 5 mg hard capsules Each hard capsule contains 5 mg of lenalidomide. Excipient with known effect Each hard capsule contains 33 mg of lactose. Lenalidomide Accord 7.5 mg hard capsules Each hard capsule contains 7.5 mg of lenalidomide. Excipient with known effect Each hard capsule contains50 mg of lactose. Lenalidomide Accord 10 mg hard capsules Each hard capsule contains 10 mg of lenalidomide. Excipientwith known effect Each hard capsule contains 67mg of lactose. Lenalidomide Accord 15 mg hard capsules Each hard capsule contains 15 mg of lenalidomide. Excipient with known effect Each hard capsule contains100 mg of lactose. Lenalidomide Accord 20 mg hard capsules Each hard capsule contains 20 mg of lenalidomide. Excipient with known effect Each hard capsule contains134 mg of lactose. Lenalidomide Accord 25 mg hard capsules Each hard capsule contains 25 mg of lenalidomide. Excipient with known effect 2 Each hard capsule contains167 mg of lactose. For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Hard capsule (capsule) Lenalidomide Accord 2.5 mg hard capsules Gelatin hard capsules size “5” approximately 11.0 mm to 11.8 mm in length, grey cap and opaque white body with “LENALIDOMIDE” printed on cap in black and “2.5 mg” printed on body in green, containing white to off white coloured powder. Lenalidomide Accord 5 mg hard capsules Gelatin hard capsules size “5” approximately 11.0 mm to 11.8 mm in length, opaque white cap and body with “LENALIDOMIDE” printed on cap in black and “5 mg” printed on body in green, containing white to off white coloured powder. Lenalidomide Accord 7.5 mg hard capsules Gelatin hard capsules size “4” approximately 14.0 mm to 14.8 mm in length, opaque lavender cap and opaque white body with “LENALIDOMIDE” printed on cap in black and “7.5 mg” printed on body in green, containing white to off white coloured powder. Lenalidomide Accord 10 mg hard capsules Gelatin hard capsules size “3” approximately 15.4 mm to 16.2 mm in length, leaf green cap and opaque white body with “LENALIDOMIDE” printed on cap in black and “10 mg” printed on body in green, containing white to off white coloured powder. Lenalidomide Accord 15 mg hard capsules Gelatin hard capsules size “2” approximately 17.4 mm to 18.2 mm in length, opaque orange cap and opaque white body with “LENALIDOMIDE” printed on cap in black and “15 mg” printed on body in green, containing white to off white coloured powder. Lenalidomide Accord 20 mg hard capsules Gelatin hard capsules size “1” approximately 19.0 mm to 19.8 mm in length, opaque green cap and opaque white body with “LENALIDOMIDE” printed on cap in black and “20 mg” printed on body in green, containing white to off white coloured powder. Lenalidomide Accord 25 mg hard capsules Gelatin hard capsules size “0” approximately 21.0 mm to 21.8 mm in length, white opaque cap and body with “LENALIDOMIDE” printed on cap in black and “25 mg” printed on body in green, containing white to off white coloured powder. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Multiple myeloma Lenalidomide Accord as monotherapy is indicated for the maintenance treatment of adult patients with newly diagnosed multiple myeloma who have undergone autologous stem cell transplantation. Lenalidomide Accord as combination therapy with dexamethasone, or bortezomib and dexamethasone, or melphalan and prednisone (see section 4.2) is indicated for the treatment of adult patients with previously untreated multiple myeloma who are not eligible for transplant. 3 Lenalidomide Accord in combination with dexamethasone is indicated for the treatment of multiple myeloma in adult patients who have received at least one prior therapy. Follicular lymphoma Lenalidomide Accord in combination with rituximab (anti-CD20 antibody) is indicated for the treatment of adult patients with previously treated follicular lymphoma (Grade 1 – 3a). 4.2 Posology and method of administration Lenalidomide treatment should be supervised by a physician experienced in the use of anti-cancer therapies. For all indications described below: Dose is modified based upon clinical and laboratory findings (see section 4.4). Dose adjustments, during treatment and restart of treatment, are recommended to manage Grade 3 or 4 thrombocytopenia, neutropenia, or other Grade 3 or 4 toxicity judged to be related to lenalidomide. In case of neutropenia, the use of growth factors in patient management should be considered. If less than 12 hours has elapsed since missing a dose, the patient can take the dose. If more than 12 hours has elapsed since missing a dose at the normal time, the patient should not take the dose, but take the next dose at the normal time on the following day. Posology Newly diagnosed multiple myeloma (NDMM) Lenalidomide maintenance in patients who have undergone autologous stem cell transplantation (ASCT) Lenalidomide maintenance should be initiated after adequate haematologic recovery following ASCT in patients without evidence of progression. Lenalidomide must not be started if the Absolute Neutrophil Count (ANC) is < 1.0 x 109/L, and/or platelet counts are < 75 x 109/L. Recommended dose The recommended starting dose is lenalidomide 10 mg orally once daily continuously (on days 1 to 28 of repeated 28-day cycles) given until disease progression or intolerance. After 3 cycles of lenalidomide maintenance, the dose can be increased to 15 mg orally once daily if tolerated. Dose reduction steps Starting dose (10 mg) If dose increased (15 mg) a Dose level -1 5 mg 10 mg Dose level -2 5 mg (days 1-21 every 28 days) 5 mg Dose level -3 Not applicable 5 mg (days 1-21 every 28 days) Do not dose below 5 mg (days 1-21 every 28 days) a After 3 cycles of lenalidomide maintenance, the dose can be increased to 15 mg orally once daily if tolerated. Thrombocytopenia When platelets Recommended course Falls to < 30 x 109/L Interrupt lenalidomide treatment Returns to ≥ 30 x 109/L Resume lenalidomide at dose level -1 once daily For each subsequent drop below 30 x 109/L Interrupt lenalidomide treatment Returns to ≥ 30 x 109/L Resume lenalidomide at next lower dose level once daily Absolute neutrophil count (ANC)-neutropenia When ANC Recommended coursea Falls to < 0.5 x 109/L Interrupt lenalidomide treatment Returns to ≥ 0.5 x 109/L Resume lenalidomide at dose level -1 once 4 When ANC Recommended coursea daily For each subsequent drop below < 0.5 x 109/L Interrupt lenalidomide treatment Returns to ≥ 0.5 x 109/L Resume lenalidomide at next lower dose level once daily a At the physician’s discretion, if neutropenia is the only toxicity at any dose level, add granulocyte colony stimulating factor (G-CSF) and maintain the dose level of lenalidomide. Lenalidomide in combination with dexamethasone until disease progression in patients who are not eligible for transplant Lenalidomide treatment must not be started if the ANC is < 1.0 x 109/L, and/or platelet counts are < 50 x 109/L. Recommended dose The recommended starting dose of lenalidomide is 25 mg orally once daily on days 1 to 21 of repeated 28-day cycles. The recommended dose of dexamethasone is 40 mg orally once daily on days 1, 8, 15 and 22 of repeated 28-day cycles. Patients may continue lenalidomide and dexamethasone therapy until disease progression or intolerance. Dose reduction steps Lenalidomidea Dexamethasonea Starting dose 25 mg 40 mg Dose level -1 20 mg 20 mg Dose level -2 15 mg 12 mg Dose level -3 10 mg 8 mg Dose level- 4 5 mg 4 mg Dose level -5 2.5 mg Not applicable ª Dose reduction for both medicinal products can be managed independently Thrombocytopenia When platelets Recommended course Falls to < 25 x 109/L Stop lenalidomide dosing for remainder of cycleª Returns to ≥ 50 x 109/L Decrease by one dose level when dosing resumed at next cycle ª If Dose limiting toxicity (DLT) occurs on > day15 of a cycle, lenalidomide dosing will be interrupted for at least the remainder of the current 28-day cycle. Absolute neutrophil count (ANC) - neutropenia When ANC Recommended course First falls to < 0.5 x 109/L Interrupt lenalidomide treatment Returns to ≥ 1 x 109/L when neutropenia is the only Resume lenalidomide at starting dose once observed toxicity daily Returns to ≥ 0.5 x 109/L when dose-dependent Resume lenalidomide at dose level -1 once haematological toxicities other than neutropenia are daily observed For each subsequent drop below < 0.5 x 109/L Interrupt lenalidomide treatment Returns to ≥ 0.5 x 109/L Resume lenalidomide at next lower dose level once daily. a At the physician’s discretion, if neutropenia is the only toxicity at any dose level, add granulocyte colony stimulating factor (G-CSF) and maintain the dose level of lenalidomide. For hematologic toxicity the dose of lenalidomide may be re-introduced to the next higher dose level (up to the starting dose) upon improvement in bone marrow function (no hematologic toxicity for at least 2 consecutive cycles: ANC ≥1,5 x 109/L with a platelet count ≥ 100 x 109/L at the beginning of a new cycle).